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1. Potential Applications of Artificial Intelligence and Machine Learning in Radiochemistry and Radiochemical Engineering

Author

Webb, E. William and Scott, Peter J. H.

Subjects
Computer Science - Machine Learning
Abstract

Artificial intelligence and machine learning are poised to disrupt PET imaging from bench to clinic. In this perspective we offer insights into how the technology could be applied to improve the design and synthesis of new radiopharmaceuticals for PET imaging, including identification of an optimal labeling approach as well as strategies for radiolabeling reaction optimization., Comment: 10 pages, 4 figures

Published
2021

4. Automated Radiosynthesis of [ 18 F]FluoFAPI and Its Dosimetry and Single Acute Dose Toxicological Evaluation.

Author

Witek, Jason A., Brooks, Allen F., Kapila, Sahil M., Winton, Wade P., Stauff, Jenelle R., Scott, Peter J. H., and Viglianti, Benjamin L.

Subjects
RADIATION dosimetry, SMALL molecules, FIBROBLASTS, RADIOISOTOPES, TIN
Abstract

Background: Cancer-associated fibroblasts have become a new target for therapy. Fibroblasts present within malignancies express the fibroblast activation protein (FAP). Inhibitors to FAP (FAPI) are small molecules recently developed as a theranostic agents for imaging and radiotherapy. All currently used FAPI rely on a linker–chelator complex attached to the 'inhibitor'. We describe a new automated method of the direct attachment of the radioisotope to the inhibitor, resulting in a >50% MW reduction with the hope of an improved tumor-to-background ratio and tumor uptake. Methods: [18F]FluroFAPI was developed from a Sn precursor. This allowed for subsequent automated radioflourination. We obtained the biodistribution of [18F]FluroFAPI in rats, performed estimated human radiation dosimetry, and performed a 100× expected single dose toxicology analysis for eventual first-in-human experiments. Results: The synthesis of the Sn precursor for FluorFAPI and the automated synthesis of [18F]FluroFAPI was demonstrated. [18F]FluroFAPI had favorable estimated human radiation dosimetry, and demonstrated no adverse effects when injected at a dose of 100× that planned for [18F]FluroFAPI. Conclusions: With the successful development of an automated synthesis of [18F]FluroFAPI, first-in-human testing can be planned with the hope of an improved tumor-to-background performance compared to other FAPI agents. [ABSTRACT FROM AUTHOR]

Published
2024
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6. C–H Labeling with [18F]Fluoride: An Emerging Methodology in Radiochemistry

Author

Wright, Jay S., Sharninghausen, Liam S., Lapsys, Alex, Sanford, Melanie S., and Scott, Peter J. H.

Abstract

Fluorine-18 is the most routinely employed radioisotope for positron emission tomography, a dynamic nuclear imaging modality. The radiolabeling of C–H bonds is an attractive method for installing fluorine-18 into organic molecules since it can preclude the cumbersome prefunctionalization of requisite precursors. Although electrophilic “F+” reagents (e.g., [18F]F2) are effective for C–H radiolabeling, state-of-the-art methodologies predominantly leverage high molar activity nucleophilic [18F]fluoride sources (e.g., [18F]KF) with substantial (pre)clinical advantages. Reflecting this, multiple nucleophilic C–H radiolabeling techniques of high utility have been disclosed over the past decade. However, the adoption of (pre)clinical C–H radiolabeling has been slow, and PET imaging agents are still routinely prepared via methods that, despite a high level of practicality, are limited in scope (e.g., SNAr, SN2 radiofluorinations). By addressing the drawbacks inherent to these strategies, C–H radiofluorination and radiofluoroalkylation carry the potential to complement and supersede state-of-the-art labeling methods, facilitating the expedited production of PET agents used in disease staging and drug development. In this Outlook, we showcase recent C–H labeling developments with fluorine-18 and discuss the merits, potential, and barriers to adoption in (pre)clinical settings. In addition, we highlight trends, challenges, and directions in this emerging field of study.

Published
2024
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9. Highlight selection of radiochemistry and radiopharmacy developments by editorial board

Author

Aime, Silvio, Al-Qahtani, Mohammed, Behe, Martin, Bormans, Guy, Carlucci, Giuseppe, DaSilva, Jean N., Decristoforo, Clemens, Duatti, Adriano, Elsinga, Philip H., Kopka, Klaus, Li, Xiang-Guo, Liu, Zhibo, Mach, Robert H., Middel, Oskar, Passchier, Jan, Patt, Marianne, Penuelas, Ivan, Rey, Ana, Scott, Peter J. H., Todde, Sergio, Toyohara, Jun, Vugts, Danielle, and Yang, Zhi

Published
2021
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12. Use of 55 PET radiotracers under approval of a Radioactive Drug Research Committee (RDRC)

Author

Jackson, Isaac M., Lee, So Jeong, Sowa, Alexandra R., Rodnick, Melissa E., Bruton, Laura, Clark, Mara, Preshlock, Sean, Rothley, Jill, Rogers, Virginia E., Botti, Leslie E., Henderson, Bradford D., Hockley, Brian G., Torres, Jovany, Raffel, David M., Brooks, Allen F., Frey, Kirk A., Kilbourn, Michael R., Koeppe, Robert A., Shao, Xia, and Scott, Peter J. H.

Published
2020
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14. Perfluoroalkanesulfonyl linker units for solid phase organic synthesis

Author

Scott, Peter J. H.

Subjects
547.2
Abstract

Diversity linker units exploit the cleavage step in solid phase synthesis for the incorporation of further diversity into target molecules. A solid-supported perfluorosulfonyl linker unit would allow cleavage of substrates using transition-metal- catalysed cross-coupling reactions. This thesis describes several approaches towards a perfluoroalkanesulfonyl diversity linker from diiodoperfluoroalkanes. Early work concentrated on the reaction of diiodoperfluoroalkanes with eugenol. The resulting perfluoroalkyliodides were attached to Wang resin using Mitsunobu chemistry. However, stability problems prevented the generation of resin bound perfluoroalkanesulfonic acids and the route was abandoned. A bis-perfluoroalkanesulfonyl chloride linker unit was prepared from diiodoperfluoroalkanes by generation of the bis-sodium sulfite salt and subsequent chlorination. Optimisation studies using design software allowed preparation of multigram quantities in 60 - 70% yield. Model solution phase synthesis of bis- perfluoroalkanesulfonamides and bis-perfluoroalkanesulfonate esters showed the feasibility of attaching the bis-sulfonyl chloride to amino resins and loading phenols. Diversity cleavage was demonstrated using Suzuki and Stille reactions and optimised by screening parallel arrays of reaction conditions. Loading the bis-sulfonyl chloride onto TentaGel® gave access to solid supported porfluorosulfonate osters and diversity cleavage was shown using Suzuki reactions. However, the linkage to solid supports proved to be unstable and an additional spacer unit was required if the linker was to find widespread use. To this end, a second generation perfluoroalkanesulfonyl linker unit was developed from ally I alcohol and diiodoperfluoroalkanes. Oxidation to a perfluoroalkanesulfonyl chloride was achieved using a novel reaction employing N- chlorosuccinimide. Several methods for loading this linker unit onto a solid support were investigated but none were successful and this chemistry requires further development before it offers a practical perfluoroalkanesulfonyl diversity linker.

Published
2004

16. GABA A Receptor Benzodiazepine Binding Sites and Motor Impairments in Parkinson's Disease.

Author

Bohnen, Nicolaas I., Barr, Jaimie, Vangel, Robert, Roytman, Stiven, Paalanen, Rebecca, Frey, Kirk A., Scott, Peter J. H., and Kanel, Prabesh

Subjects
GABA receptors, PARKINSON'S disease, BINDING sites, BENZODIAZEPINE receptors, MONOAMINE transporters
Abstract

Flumazenil is an allosteric modulator of the γ-aminobutyric acid-A receptor (GABAAR) benzodiazepine binding site that could normalize neuronal signaling and improve motor impairments in Parkinson's disease (PD). Little is known about how regional GABAAR availability affects motor symptoms. We investigated the relationship between regional availability of GABAAR benzodiazepine binding sites and motor impairments in PD. Methods: A total of 11 Patients with PD (males; mean age 69.0 ± 4.6 years; Hoehn and Yahr stages 2–3) underwent [11C]flumazenil GABAAR benzodiazepine binding site and [11C]dihydrotetrabenazine vesicular monoamine transporter type-2 (VMAT2) PET imaging and clinical assessment. Stepwise regression analysis was used to predict regional cerebral correlates of the four cardinal UPDRS motor scores using cortical, striatal, thalamic, and cerebellar flumazenil binding estimates. Thalamic GABAAR availability was selectively associated with axial motor scores (R2 = 0.55, F = 11.0, β = −6.4, p = 0.0009). Multi-ligand analysis demonstrated significant axial motor predictor effects by both thalamic GABAAR availability (R2 = 0.47, β = −5.2, F = 7.2, p = 0.028) and striatal VMAT2 binding (R2 = 0.30, β = −3.9, F = 9.1, p = 0.019; total model: R2 = 0.77, F = 11.9, p = 0.0056). Post hoc analysis demonstrated that thalamic [11C]methyl-4-piperidinyl propionate cholinesterase PET and K1 flow delivery findings were not significant confounders. Findings suggest that reduced thalamic GABAAR availability correlates with worsened axial motor impairments in PD, independent of nigrostriatal degeneration. These findings may augur novel non-dopaminergic approaches to treating axial motor impairments in PD. [ABSTRACT FROM AUTHOR]

Published
2023
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20. Preparation and Evaluation of 64Cu-Radiolabled Dual-Ligand Multifunctional Gold Nanoparticles for Tumor Theragnosis

Author

Mhanna, Karim, primary, Qian, Wei, additional, Zhong, Ziyun, additional, Brooks, Allen F., additional, Ouchi, Erika, additional, Stauff, Jenelle, additional, Arteaga, Janna, additional, Papachristou, Maria, additional, Datseris, Ioannis E., additional, Liu, Bing, additional, Shao, Xia, additional, and Scott, Peter J. H., additional

Published
2023
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25. SNMMI Clinical Trial Network Research Series for Technologists: Application of Good Clinical Practice to Clinical Research in Medical Imaging.

Author

Trembath, LisaAnn, Frye, Sarah A., Scott, Peter J. H., and Hoffman, John M.

Abstract

This manuscript is part of a series developed by the Clinical Trials Network (CTN) of the Society of Nuclear Medicine and Molecular Imaging (SNMMI) to offer training and information for molecular imaging technologists and researchers about various aspects of clinical research. This article covers the topic of Good Clinical Practice, and how that relates to the Code of Federal Regulations that govern clinical research in the US such as 21CFR§312 and the Common Rule. The purpose of this article is to inform technologists and researchers about standard roles, documents, guidance, and processes that are elemental to the conduct of clinical trials, and to offer additional resources for learning about these processes. [ABSTRACT FROM AUTHOR]

Published
2023
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26. Preparation and Evaluation of 64 Cu-Radiolabled Dual-Ligand Multifunctional Gold Nanoparticles for Tumor Theragnosis.

Author

Mhanna, Karim, Qian, Wei, Zhong, Ziyun, Brooks, Allen F., Ouchi, Erika, Stauff, Jenelle, Arteaga, Janna, Papachristou, Maria, Datseris, Ioannis E., Liu, Bing, Shao, Xia, and Scott, Peter J. H.

Subjects
GOLD nanoparticles, RADIOACTIVE tracers, BIOMOLECULES, FEMTOSECOND lasers, PULSED lasers, LASER ablation, ARGININE
Abstract

Gold nanoparticles (AuNPs) are cutting-edge platforms for combined diagnostic and therapeutic approaches due to their exquisite physicochemical and optical properties. Using the AuNPs physically produced by femtosecond pulsed laser ablation of bulk Au in deionized water, with a capping agent-free surface, the conjugation of functional ligands onto the AuNPs can be tunable between 0% and 100% coverage. By taking advantage of this property, AuNPs functionalized by two different types of active targeting ligands with predetermined ratios were fabricated. The quantitatively controllable conjugation to construct a mixed monolayer of multiple biological molecules at a certain ratio onto the surface of AuNPs was achieved and a chelator-free 64Cu-labeling method was developed. We report here the manufacture, radiosynthesis and bioevaluation of three different types of dual-ligand AuNPs functionalized with two distinct ligands selected from glucose, arginine–glycine–aspartate (RGD) peptide, and methotrexate (MTX) for tumor theragnosis. The preclinical evaluation demonstrated that tumor uptakes and retention of two components AuNP conjugates were higher than that of single-component AuNP conjugates. Notably, the glucose/MT- modified dual-ligand AuNP conjugates showed significant improvement in tumor uptake and retention. The novel nanoconjugates prepared in this study make it possible to integrate several modalities with a single AuNP for multimodality imaging and therapy, combining the power of chemo-, thermal- and radiation therapies together. [ABSTRACT FROM AUTHOR]

Published
2023
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27. Automated Synthesis of 18F-BCPP-EF {2-tert-Butyl-4-Chloro-5-{6-[2-(2[18F]fluoroethoxy)-Ethoxy]-Pyridin-3-ylmethoxy}-2H-Pyridazin-3-One for Imaging of Mitochondrial Complex 1 in Parkinson’s Disease

Author

Kaur, Tanpreet, primary, Brooks, Allen F., additional, Liddell, Katherine M., additional, Henderson, Bradford D., additional, Hockley, Brian G., additional, Bohnen, Nicolaas I., additional, Albin, Roger L., additional, and Scott, Peter J. H., additional

Published
2022
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34. On the consensus nomenclature rules for radiopharmaceutical chemistry - Reconsideration of radiochemical conversion

Author

Herth, Matthias M., Ametamey, Simon, Antuganov, Dmitrii, Bauman, Andreas, Berndt, Mathias, Brooks, Allen F., Bormans, Guy, Choe, Yearn Seong, Gillings, Nic, Hafeli, Urs O., James, Michelle L., Kopka, Klaus, Kramer, Vasko, Krasikova, Raisa, Madsen, Jacob, Mu, Linjing, Neumaier, Bernd, Piel, Markus, Roesch, Frank, Ross, Tobias, Schibli, Roger, Scott, Peter J. H., Shalgunov, Vladimir, Vasdev, Neil, Wadsak, Wolfgang, Zeglis, Brian M., Herth, Matthias M., Ametamey, Simon, Antuganov, Dmitrii, Bauman, Andreas, Berndt, Mathias, Brooks, Allen F., Bormans, Guy, Choe, Yearn Seong, Gillings, Nic, Hafeli, Urs O., James, Michelle L., Kopka, Klaus, Kramer, Vasko, Krasikova, Raisa, Madsen, Jacob, Mu, Linjing, Neumaier, Bernd, Piel, Markus, Roesch, Frank, Ross, Tobias, Schibli, Roger, Scott, Peter J. H., Shalgunov, Vladimir, Vasdev, Neil, Wadsak, Wolfgang, and Zeglis, Brian M.

Abstract

Radiochemical conversion is an important term to be included in the "Consensus nomenclature rules for radiopharmaceutical chemistry". Radiochemical conversion should be used to define reaction efficiency by measuring the transformation of components in a crude reaction mixture at a given time, whereas radiochemical yield is better suited to define the efficiency of an entire reaction process including, for example, separation, isolation, filtration, and formulation. (C) 2020 Elsevier Inc. All rights reserved.

Published
2021

36. Additional file 1 of Use of 55 PET radiotracers under approval of a Radioactive Drug Research Committee (RDRC)

Author

Jackson, Isaac M., Lee, So Jeong, Sowa, Alexandra R., Rodnick, Melissa E., Bruton, Laura, Clark, Mara, Preshlock, Sean, Rothley, Jill, Rogers, Virginia E., Botti, Leslie E., Henderson, Bradford D., Hockley, Brian G., Jovany Torres, Raffel, David M., Brooks, Allen F., Frey, Kirk A., Kilbourn, Michael R., Koeppe, Robert A., Shao, Xia, and Scott, Peter J. H.

Subjects
Data_FILES
Abstract

Additional file 1.

Published
2020
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37. Radionuclide Imaging for Neuroscience:Current Opinion and Future Directions

Author

Gee, Antony D., Herth, Matthias M., James, Michelle L., Korde, Aruna, Scott, Peter J. H., Vasdev, Neil, Gee, Antony D., Herth, Matthias M., James, Michelle L., Korde, Aruna, Scott, Peter J. H., and Vasdev, Neil

Abstract

This meeting report summarizes a Consultants Meeting that was held at International Atomic Energy Agency headquarters in Vienna to provide an update on radionuclide imaging for neuroscience applications.

Published
2020

38. Training the next generation of radiopharmaceutical scientists

Author

Gee, Antony D., Andersson, Jan, Bhalla, Rajiv, Choe, Yearn Seong, Dick, David W., Herth, Matthias M., Hostetler, Eric D., Jauregui-Haza, Ulises J., Huang, Ya-Yao, James, Michelle L., Jeong, Jae Min, Korde, Aruna, Kuge, Yuji, Kung, Hank F., Lapi, Suzanne E., Osso, Joao Alberto, Parent, Ephraim, Patt, Marianne, Pricile, Ekoume Fany, Riss, Patrick J., Santos-Oliveira, Ralph, Taylor, Stephen, Vasdev, Neil, Vercouillie, Johnny, Wadsak, Wolfgang, Yang, Zhi, Zhu, Hua, Scott, Peter J. H., Gee, Antony D., Andersson, Jan, Bhalla, Rajiv, Choe, Yearn Seong, Dick, David W., Herth, Matthias M., Hostetler, Eric D., Jauregui-Haza, Ulises J., Huang, Ya-Yao, James, Michelle L., Jeong, Jae Min, Korde, Aruna, Kuge, Yuji, Kung, Hank F., Lapi, Suzanne E., Osso, Joao Alberto, Parent, Ephraim, Patt, Marianne, Pricile, Ekoume Fany, Riss, Patrick J., Santos-Oliveira, Ralph, Taylor, Stephen, Vasdev, Neil, Vercouillie, Johnny, Wadsak, Wolfgang, Yang, Zhi, Zhu, Hua, and Scott, Peter J. H.

Published
2020

41. Breakthroughs in Medicinal Chemistry: New Targets and Mechanisms, New Drugs, New Hopes–7

Author

Gütschow, Michael, primary, Vanden Eynde, Jean Jacques, additional, Jampilek, Josef, additional, Kang, CongBao, additional, Mangoni, Arduino A., additional, Fossa, Paola, additional, Karaman, Rafik, additional, Trabocchi, Andrea, additional, Scott, Peter J. H., additional, Reynisson, Jóhannes, additional, Rapposelli, Simona, additional, Galdiero, Stefania, additional, Winum, Jean-Yves, additional, Brullo, Chiara, additional, Prokai-Tatrai, Katalin, additional, Sharma, Arun K., additional, Schapira, Matthieu, additional, Azuma, Yasu-Taka, additional, Cerchia, Laura, additional, Spetea, Mariana, additional, Torri, Giangiacomo, additional, Collina, Simona, additional, Geronikaki, Athina, additional, García-Sosa, Alfonso T., additional, Vasconcelos, M. Helena, additional, Sousa, Maria Emília, additional, Kosalec, Ivan, additional, Tuccinardi, Tiziano, additional, Duarte, Iola F., additional, Salvador, Jorge A. R., additional, Bertinaria, Massimo, additional, Pellecchia, Maurizio, additional, Amato, Jussara, additional, Rastelli, Giulio, additional, Gomes, Paula A. C., additional, Guedes, Rita C., additional, Sabatier, Jean-Marc, additional, Estévez-Braun, Ana, additional, Pagano, Bruno, additional, Mangani, Stefano, additional, Ragno, Rino, additional, Kokotos, George, additional, Brindisi, Margherita, additional, González, Florenci V., additional, Borges, Fernanda, additional, Miloso, Mariarosaria, additional, Rautio, Jarkko, additional, and Muñoz-Torrero, Diego, additional

Published
2020
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45. Breakthroughs in Medicinal Chemistry: New Targets and Mechanisms, New Drugs, New Hopes–6

Author

Vanden Eynde, Jean Jacques, primary, Mangoni, Arduino A., additional, Rautio, Jarkko, additional, Leprince, Jérôme, additional, Azuma, Yasu-Taka, additional, García-Sosa, Alfonso T., additional, Hulme, Christopher, additional, Jampilek, Josef, additional, Karaman, Rafik, additional, Li, Wei, additional, Gomes, Paula A. C., additional, Hadjipavlou-Litina, Dimitra, additional, Capasso, Raffaele, additional, Geronikaki, Athina, additional, Cerchia, Laura, additional, Sabatier, Jean-Marc, additional, Ragno, Rino, additional, Tuccinardi, Tiziano, additional, Trabocchi, Andrea, additional, Winum, Jean-Yves, additional, Luque, F. Javier, additional, Prokai-Tatrai, Katalin, additional, Spetea, Mariana, additional, Gütschow, Michael, additional, Kosalec, Ivan, additional, Guillou, Catherine, additional, Vasconcelos, M. Helena, additional, Kokotos, George, additional, Rastelli, Giulio, additional, de Sousa, Maria Emília, additional, Manera, Clementina, additional, Gemma, Sandra, additional, Mangani, Stefano, additional, Siciliano, Carlo, additional, Galdiero, Stefania, additional, Liu, Hong, additional, Scott, Peter J. H., additional, de los Ríos, Cristóbal, additional, Agrofoglio, Luigi A., additional, Collina, Simona, additional, Guedes, Rita C., additional, and Muñoz-Torrero, Diego, additional

Published
2019
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46. PSMA PET validates higher rates of metastatic disease for European Association of Urology Biochemical Recurrence Risk Groups: an international multicentre study.

Author

Ferdinandus, Justin, Fendler, Wolfgang P., A., Andrea Farolfi, Washington, Samuel, Mohamad, Osama, Pampaloni, Miguel H., Scott, Peter J. H., Rodnick, Melissa, Viglianti, Benjamin L., Eiber, Matthias, Herrmann, Ken, Czernin, Johannes, Armstrong, Wesley R., Calais, Jeremie, Hope, Thomas A., and Piert, Morand

Published
2021
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48. A comprehensive assessment of 68Ga-PSMA-11 PET in biochemically recurrent prostate cancer: Results from a prospective multi-center study in 2005 patients.

Author

Abghari-Gerst, Monica, Armstrong, Wesley R., Nguyen, Kathleen, Calais, Jeremie, Czernin, Johannes, Lin, David, Jariwala, Namasvi, Rodnick, Melissa, Hope, Thomas A., Hearn, Jason, Montgomery, Jeffrey S., Alva, Ajjai, Reichert, Zachery R., Spratt, Daniel E., Johnson, Timothy D., Scott, Peter J. H., and Piert, Morand

Published
2021
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49. A comprehensive assessment of 68Ga-PSMA-11 PET in biochemically recurrent prostate cancer: Results from a prospective multi-center study in 2005 patients.

Author

Abghari-Gerst, Monica, Armstrong, Wesley R., Nguyen, Kathleen, Calais, Jeremie, Czernin, Johannes, Lin, David, Jariwala, Namasvi, Rodnick, Melissa, Hope, Thomas A., Hearn, Jason, Montgomery, Jeffrey S., Alva, Ajjai, Reichert, Zachery R., Spratt, Daniel E., Johnson, Timothy D., Scott, Peter J. H., and Piert, Morand

Published
2021
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